REVIEW ARTICLE J Surg Ultrasound 2018;5:11-17 JSU Journal of Surgical Ultrasound 갑상선암의치료에서초음파의유용성 전북대학교의과대학외과학교실유방ㆍ갑상선외과 윤현조, 강상율, 정성후 Usefulness of Ultrasound in the Management of Thyroid Carcinoma Hyun Jo Youn, Sang Yull Kang, Sung Hoo Jung Division of Breast ㆍ Thyroid Surgery, Department of Surgery, Chonbuk National University Medical School, Jeonju, Korea Received March 26, 2018 Revised April 30, 2018 Accepted May 4, 2018 Correspondence to: Sung Hoo Jung Division of Breast ㆍ Thyroid Surgery, Department of Surgery, Chonbuk National University Medical School, 567 Baekje-daero, Deokjin-gu, Jeonju 54896, Korea Tel: +82-63-250-2133 Fax: +82-63-271-6197 E-mail: shjung@jbnu.ac.kr Since the late 1960s, ultrasonography (US) has been used increasingly in the diagnosis and treatment of patients with thyroid carcinoma. As a noninvasive, rapid, and easily reproducible high-resolution imaging study, the use of US has expanded from the detection of nonpalpable thyroid carcinoma to an examination of the lymph node basins for staging purposes and treatment planning, fine needle aspiration guidance, intraoperative localization of thyroid lesions and lymph nodes, and postoperative surveillance for recurrent thyroid carcinoma. The recent literature has shown that compared to radiologist-performed US, surgeon-performed US is more accurate and suitable for thyroid carcinoma patients with lower local recurrence rates. This article reviews the clinical significance and usefulness of US in the management of patient with thyroid carcinoma. Keywords: Lymph node, Thyroid carcinoma, Ultrasonography 서론 갑상선암은국내여성암발생률 1위를차지하는암으로 2015년한해약 25,000명의새로운환자가발생했다.(1) 갑상선암의발생율이높은이유로는건강에대한관심증가로인한검진의활성화와함께갑상선초음파를포함한영상학적진단기술의발전을여러원인중의하나로꼽을수있다. 모든갑상선암의 90% 는분화갑상선암 (differentiated thyroid cancer) 이며갑상선유두암 (papillary thyroid cancer) 이대부분을차지하고있다.(2) 림프절전이는갑상선암환자의 30-80% 에서발견되며재발의가장흔한위험인자로알려져있다.(3) 신체진찰은작은크기의갑상선암이나림프절전이를발견하기에는민감도가낮아갑상선암의확실한수술전진단이 나수술후추적관찰을위해서는좀더정확한영상학적검사가필요하다. 갑상선초음파는갑상선병변을확인하는데가장흔히사용되는유용하고안전하며효율적인방법으로 American Thyroid Association과 National Comprehensive Cancer Network 등여러권위있는단체에서갑상선질환을진단하고치료하는가이드라인으로권고하고있다.(4) 과거에는갑상선을영상화하기위해방사성요오드를축적하여촬영하는갑상선스캔 (scan) 이필요하였으나초음파의출현이후고해상도의이미지, 실시간촬영, 간단하고비침습적임, 조직검사의동시시행가능, 방사선노출이없다는점등의장점으로많은임상의들이대다수의갑상선환자들에게스캔을대체하여시행하고있다.(5) 전통적으로갑상선암환자의수술전, 후병기설정을 Journal of Surgical Ultrasound is an Open Access Journal. All articles are distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright c 2018 by The Korean Surgical Ultrasound Society ISSN 2288-9140
J Surg Ultrasound Vol. 5, No. 1, 2018 위한초음파는영상의학과전문의에의해시행되어왔다. 하지만최근보고에따르면외과의사에의해시행되는초음파가영상의학과의사에의해시행되는초음파에비해좀더정확하고수술전계획을설계하는데유용하여국소재발률을낮추는것으로알려져있다.(6-8) 갑상선암의적절한치료를위해진단당시병변의범위를정확히파악하는것은필수적이다. 즉, 수술전에이미존재했던병변을발견하지못하면부적절한제거로인해수술후잔존암이발생하여재발의위험을높이고결국재수술을필요로하게된다.(4) 갑상선암의수술전진단에있어갑상선초음파는가장민감도가높은진단방법으로알려져있으며세침흡인세포검사 (fine needle aspiration cytology, FNAC) 를동시에시행할수있고수술중병변을실시간으로확인할수있으며수술후추적관찰에도매우유용한것으로보고된다.(9-11) 이에저자들은문헌고찰을통해갑상선암환자의적절한진단과치료에있어초음파의임상적중요성과유용성에관하여살펴보고자한다. 본론 1. 수술전초음파갑상선암환자의진료에있어갑상선초음파는가장기본적인영상학적검사방법으로갑상선의원발종양과함께다른종양들의존재여부와경부림프절전이여부등을평가해야한다. 악성이의심되는갑상선종양이나림프절이관찰되는경우에는초음파유도하 FNAC 를통해조직 학적으로확인후수술범위를결정한다.(12,13) 1) 갑상선결절갑상선결절은중년여성의 50% 이상에서발견되는흔한질환으로이중약 5% 만이악성결절이다.(14) 초음파검사단독으로는갑상선결절의악성여부를정확하게판명할수없지만임상의들이악성여부를판단하는데강력한단서를제공한다. 악성을시사하는갑상선결절의특징적인초음파소견으로는단단하고 (solid), 저에코성이며 (hypoechoic), 미세석회화 (microcalcification), 가장자리의왜곡 (distortion of the rim), 키큰형태 (taller than wide), 중심부혈관신생 (central vascularity), 갑상선외침범 (extrathyroidal extension) 등이있다. 경계가명확하고낭성소견을보이는갑상선결절은일반적으로양성인경우가많은반면에악성결절은경계가불명확하고단단하며주변정상갑상선실질보다저에코성을보이는경우가흔하다 (Fig. 1). 미세석회화는갑상선암환자에서 85% 의민감도, 95% 의특이도와 94% 의정확도를가진다고보고된다 (Fig. 2).(15) 그러나크고거친석회화나결절의표면을따라존재하는석회화 (rim calcification) 는모든종류의결절에서흔히볼수있는소견으로이전의출혈이나퇴행성변화를반영하기도한다. 최근에보고된체계적고찰에서키큰형태를보이는결절의악성민감도와특이도는각각 53% 와 93% 였으며, 특히크기가큰결절에서는민감도가낮은것으로알려져있다.(16,17) 혈류분포의양상도악성갑상선결절을예측하는인자로알려져있으며결절중앙부분에혈류가증가하는소견이결절주변부에서보이는혈관생성보다악성일가능성이높다.(18) 갑상선초음파상갑상선암을시사 Fig. 1. Right papillary carcinoma in a 48-year-old woman. Transverse gray-scale ultrasonographic image demonstrates that the nodule is 0.6 0.4 cm sized, hypoechoic, irregular margin and taller than wide. Fig. 2. Right papillary carcinoma in a 35-year-old man. Sagittal gray-scale ultrasonographic image shows microcalcifications in a 1.4 1.3 cm sized, hypoechoic and solid nodule. 12
Hyun Jo Youn, et al.: Ultrasound in Thyroid Cancer 하는특징적인단일소견은없지만앞서살펴본여러특징들을함께보이는갑상선결절인경우에악성의가능성이매우높아진다.(19,20) 갑상선결절의양성과악성을시사하는특징적인소견을 Table 1에정리하였다. 갑상선암의대부분을차지하는갑상성유두암은다병소성 (multifocality) 의특징이있기때문에갑상선암환자에서다발성결절은적절한수술계획을수립하기위해주의깊게살펴야한다. 크기가 1 cm 이상인결절은더욱세밀하게평가해야하며악성을시사하는초음파소견을보이는경우 FNAC 를적극적으로시행해악성여부를판단해야한다. 특히의심스러운결절이양측에있다면향후갑상선전절제술을시행해야할수있으므로원발병소반대측엽에결절이있는경우확실히평가해야한다. 136명의갑상선암환자를대상으로연구한보고 (7) 에따르면영상의학과의사가시행한갑상선초음파의 22% 에서반대측결절을간과하였으며, 또다른연구에서도영상의학과의사가놓친반대측결절을외과의사가발견하여적절한치료를시행할수있었다고보고하였다.(6) 갑상선암환 Table 1. Ultrasonographic Features Associated with Benign and Malignant Thyroid Nodules Feature Benign Malignant Echogenicity Isoechoic Hypoechoic Calcification Large, coarse Micro Margin Smooth Irregular Shape Wider than tall Taller than wide Vascularity Peripheral Central 자의수술전초음파에서반대측결절의악성여부판단은갑상선전절제술시행여부를결정하는매우중요한인자이므로항상세밀하게관찰해야한다. 갑상선외침범은갑상선암환자의국소재발과전이의위험인자로알려져있다.(21) 수술전갑상선외침범 ( 특히뒤쪽침범으로인한신경, 기도, 식도등의주요기관침습 ) 을정확하게예측하지못하면좀더복잡한수술술기를시행하는데어려움을겪을수있으며, 수술후재발의위험을증가시킬수있다. 따라서수술을직접집도하는외과의사는수술전초음파에서갑상선암의갑상선외침범여부를반드시주의깊게살펴야한다 (Fig. 3). 2) 림프절분화성갑상선암환자의약 20-50% 에서경부림프절전이가보고되므로수술전명확한병기설정을위해경부림프절의전이여부평가가매우중요하다.(22) 전이된림프절을시사하는초음파의특징적인소견으로는낭성변화 (cystic degeneration), 미세석회화, 주변부혈류증가, 주변근육과비교해고에코성, 지방문의소실 (loss of fatty hilum), 둥근형태등이있다 (Fig. 4). (23,24) 이중낭성변화와미세석회화는가장높은특이도를보이며림프절전이소견이있는경우즉각적인 FNAC 를시행해야한다.(25) 초음파의악성경부림프절의민감도와특이도는각각 94.4% 와 85.2% 로보고된다.(5) 갑상선암환자의수술후남아있는전이림프절은재발 Fig. 3. Extrathyroidal extension of a right papillary carcinoma in a 47-year-old woman. Transverse gray-scale ultrasonographic image demonstrates a 1.2 cm sized, hypoechoic and solid nodule with indistinct lateral margins and invasion of the adjacent tissue which was confirmed intraoperatively. Fig. 4. Metastatic left level II lymph node in a 58-year-old man with left papillary thyroid carcinoma. Transverse gray-scale ultrasonographic image demonstrates an enlarged (1.0 cm sized) left level II lymph node with an abnormally thickened, irregular margin and loss of the fatty hilum. 13
J Surg Ultrasound Vol. 5, No. 1, 2018 의가장흔한원인이며불완전한수술전검사를의미하기도한다. 예방적중앙경부림프절절제술의유용성에대하여아직이견이많은상황에수술전중앙경부림프절의확인은매우중요하며, 초음파판독지에이에관한기술도필수적이다. 그럼에도불구하고갑상선암환자를대상으로영상의학과의사에의해시행된초음파에서경부림프절에대한평가와기술이많이부족했다는보고가있어,(8) 수술전초음파에서경부림프절의전이여부를명확히판단함으로써적절한수술과이에따른예후증진에기여할수있을것으로생각한다. 3) 초음파유도하세침흡인세포검사초음파상악성을시사하는소견이많은갑상선결절이나림프절의정확한진단을위해서는 FNAC 가필수적이다.(23) 과거에 FNAC는주로촉지되는결절에서시행되었으나초음파유도하 FNAC를통해촉지되지않는작은결절에서도정확한조직검사가가능하게되었다. 초음파유도하 FNAC 는바늘의위치를확인하며조직검사를시행할수있어부적절한검체획득을줄이고민감도와특이도를증가시키는장점이있다.(26,27) 초음파유도하 FNAC의정확도는 91-93% 로보고되고있으며, 흡인된검체에서티로글로불린 (thyroglobulin) 을측정하거나유전자돌연변이 (gene mutation) 또는 mrna 발현등을살펴봄으로써진단의정확도를향상시킬수있다.(28-30) 2. 수술중초음파갑상선암환자에서수술중초음파 (intraoperative ultrasonography, IOUS) 는매우유용하여수술의완결성을향상시키고특히경부림프절재발병변의위치결정에탁월한장점이있다. 갑상선암환자의수술시 IOUS 를시행한군에서시행하지않은군에비해통계학적으로의미있게낮은재발률을보였으며 (1.9% vs. 12.5%, P<0.05),(31) Agcaoglu 등 (32) 은갑상선암환자중변형근치경부절제술을시행하는 25명의환자를대상으로 IOUS 를적용하였을때 4예 (16%) 에서 IOUS 를통해 II, IV와 V 구역에서잔존하는림프절을찾아절제함으로써수술의완결성을높일수있었다고보고하였다. 갑상선암의경부림프절전이시수술적절제가표준치료인데이전수술에의한유착및반흔 (scar) 조직에의해병변의정확한제거가어려운경우가있다. 따라서재수술시에는첫수술보다후두신경과부갑상선의손상등의합병증발생률이높으며수술시간도더오래걸리는것으로알려져있다.(33) 재발갑상선암환자에서 IOUS는매우유용하며중앙경부림프절전이와병변의크기가 2 cm 미만인경우그리고이전에외부방사선조사를받은경우에특히효과적이다.(34) 재발갑상선암환자에서병변의 IOUS 유도하생체염료주입은수술실에서외과의사가직접시행하는경우수술시목표병변의위치를가늠하는데매우효과적이며, 또한절제된병변의동결절편검사를시행하지않아도되기때문에수술시간및의료비용을절약할수있는장점도있다 (Fig. 5).(35) Fig. 5. Injection of vital dye during intraoperative ultrasonography in a 51-year-old woman with recurrent papillary thyroid carcinoma. (A) Intraoperative ultrasonography-guided vital dye injection to recurrent cervical lymph node. (B) The needle (arrow) was inserted to the 0.7 cm sized lymph node located in right level III. 14
Hyun Jo Youn, et al.: Ultrasound in Thyroid Cancer 3. 수술후초음파역사적으로분화성갑상선암환자의수술후재발여부감시는혈중티로글로불린과전신스캔으로이루어졌다. 하지만전신스캔의민감도가낮은것이알려지면서실제임상에서는혈중티로글로불린과초음파를주로사용하고있으며재발병변에대해 96.3% 의민감도와 99.5% 의음성예측도를보이고있다.(36) 갑상선암환자의수술후재발은경부와종격동림프절 (74%), 갑상선수술부위 (bed) (20%), 기도또는인접근육 (6%) 의순으로발생한다.(37) 이러한재발들은일반적으로촉지되지않는작은병변으로나타나기때문에수술후추적관찰에서초음파는매우중요한역할을담당한다.(38,39) 정상적으로갑상선수술부위는섬유지방증식성조직 (fibrofatty proliferative tissue) 으로채워지기때문에잔존하는정상갑상선조직과재발병변과의주의깊은감별을요한다. 갑상선수술부위에서재발한결절의초음파소견은수술전결절과비슷하여불규칙한경계, 저에코성, 미세석회화, 키큰형태등의특징이있다.(40) 그러나이러한병변은수술후육아종, 신경종, 반응성림프절또는부갑상선선종등과감별을요한다.(24) 경부림프절 ( 특히 II-VI 구역 ) 은갑상선암환자의가장흔한재발부위이므로수술후초음파로주의깊게살펴야한다. 전이림프절을의심할수있는크기가보고되고있지만 (II 구역은 0.8 cm 이상, III-VI 구역은 0.5 cm 이상 ) 림프절의크기만으로는악성림프절을예측할수있는정확도가낮아수술전과유사한전이림프절을시사하는초음파소견을보이는림프절은 FNAC를통해재발여부를판단해야한다.(37) 갑상선엽절제술을시행받은환자의경우수술후혈중티로글로불린을재발예측인자로활용할수없기때문에수술후추적관찰시갑상선초음파의유용성은더욱높아진다.(41) 갑상선암환자의수술또는방사선요오드치료후초음파추적관찰은 6-12개월째에시작하며그이후환자의재발위험도에따라정기적인간격으로시행한다.(41) 향후갑상선암환자의수술후재발감시를위한초음파의적절한시행시기를결정하기위한추가적인연구가필요하다. 결 론 갑상선암환자의진료에서초음파는필수적인영상학적진단방법으로진단, 병기설정, 수술범위결정, 수술의완결성, 수술후추적검사등에다양하게적용된다. 갑상선수술을집도하는외과의는보다나은양질의진료를위해초음파를능숙하게사용하는능력을배양해야한다. 향후발전된초음파의적용을통해갑상선암환자의진단및치료정확도를높임으로써궁극적으로갑상선암환자의삶의질을향상시킬수있을것으로생각한다. REFERENCES 1. National Cancer Information Center. Cancer statistics [Internet]. Goyang: Ministry of Health and Welfare [cited 2018 Mar 14]. Available from http://www. cancer.go.kr. 2. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin 2014;64:9-29. 3. Stack BC Jr, Ferris RL, Goldenberg D, Haymart M, Shaha A, Sheth S, et al. American Thyroid Association consensus review and statement regarding the anatomy, terminology, and rationale for lateral neck dissection in differentiated thyroid cancer. Thyroid 2012;22:501-8. 4. Yeh MW, Bauer AJ, Bernet VA, Ferris RL, Loevner LA, Mandel SJ, et al. American Thyroid Association statement on preoperative imaging for thyroid cancer surgery. Thyroid 2015;25:3-14. 5. Sipos JA. Advances in ultrasound for the diagnosis and management of thyroid cancer. Thyroid 2009;19: 1363-72. 6. Mazzaglia PJ. Surgeon-performed ultrasound in patients referred for thyroid disease improves patient care by minimizing performance of unnecessary procedures and optimizing surgical treatment. World J Surg 2010;34:1164-70. 7. Carneiro-Pla D, Amin S. Comparison between preconsultation ultrasonography and office surgeonperformed ultrasound in patients with thyroid cancer. World J Surg 2014;38:622-7. 8. Oltmann SC, Schneider DF, Chen H, Sippel RS. All thyroid ultrasound evaluations are not equal: sonographers specialized in thyroid cancer correctly label clinical N0 disease in well differentiated thyroid cancer. Ann Surg Oncol 2015;22:422-8. 9. Milas M, Stephen A, Berber E, Wagner K, Miskulin J, Siperstein A. Ultrasonography for the endocrine surgeon: a valuable clinical tool that enhances diagnostic and therapeutic outcomes. Surgery 2005;138:1193-15
J Surg Ultrasound Vol. 5, No. 1, 2018 200; discussion 1200-1. 10. O Connell K, Yen TW, Quiroz F, Evans DB, Wang TS. The utility of routine preoperative cervical ultrasonography in patients undergoing thyroidectomy for differentiated thyroid cancer. Surgery 2013;154:697-701; discussion 701-3. 11. Lew JI, Solorzano CC. Use of ultrasound in the management of thyroid cancer. Oncologist 2010;15:253-8. 12. Kouvaraki MA, Shapiro SE, Fornage BD, Edeiken- Monro BS, Sherman SI, Vassilopoulou-Sellin R, et al. Role of preoperative ultrasonography in the surgical management of patients with thyroid cancer. Surgery 2003;134:946-54; discussion 954-5. 13. Park JS, Son KR, Na DG, Kim E, Kim S. Performance of preoperative sonographic staging of papillary thyroid carcinoma based on the sixth edition of the AJCC/UICC TNM classification system. AJR Am J Roentgenol 2009;192:66-72. 14. Caruso D, Mazzaferri EL. Fine needle aspiration biopsy in the management of thyroid nodules. Endocrinol 1991;1:194-202. 15. Salmaslioğlu A, Erbil Y, Dural C, Işsever H, Kapran Y, Ozarmağan S, et al. Predictive value of sonographic features in preoperative evaluation of malignant thyroid nodules in a multinodular goiter. World J Surg 2008;32:1948-54. 16. Brito JP, Gionfriddo MR, Al Nofal A, Boehmer KR, Leppin AL, Reading C, et al. The accuracy of thyroid nodule ultrasound to predict thyroid cancer: systematic review and meta-analysis. J Clin Endocrinol Metab 2014;99:1253-63. 17. Ren J, Liu B, Zhang LL, Li HY, Zhang F, Li S, et al. A taller-than-wide shape is a good predictor of papillary thyroid carcinoma in small solid nodules. J Ultrasound Med 2015;34:19-26. 18. Cappelli C, Castellano M, Pirola I, Cumetti D, Agosti B, Gandossi E, et al. The predictive value of ultrasound findings in the management of thyroid nodules. QJM 2007;100:29-35. 19. Méndez W, Rodgers SE, Lew JI, Montano R, Solórzano CC. Role of surgeon-performed ultrasound in predicting malignancy in patients with indeterminate thyroid nodules. Ann Surg Oncol 2008;15:2487-92. 20. Jabiev AA, Ikeda MH, Reis IM, Solorzano CC, Lew JI. Surgeon-performed ultrasound can predict differentiated thyroid cancer in patients with solitary thyroid nodules. Ann Surg Oncol 2009;16:3140-5. 21. Andersen PE, Kinsella J, Loree TR, Shaha AR, Shah JP. Differentiated carcinoma of the thyroid with extrathyroidal extension. Am J Surg 1995;170:467-70. 22. Chow SM, Law SC, Chan JK, Au SK, Yau S, Lau WH. Papillary microcarcinoma of the thyroid-prognostic significance of lymph node metastasis and multifocality. Cancer 2003;98:31-40. 23. Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, et al. 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: The American Thyroid Association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid 2016;26:1-133. 24. Leenhardt L, Erdogan MF, Hegedus L, Mandel SJ, Paschke R, Rago T, et al. 2013 European Thyroid Association guidelines for cervical ultrasound scan and ultrasound-guided techniques in the postoperative management of patients with thyroid cancer. Eur Thyroid J 2013;2:147-59. 25. Leboulleux S, Girard E, Rose M, Travagli JP, Sabbah N, Caillou B. Ultrasound criteria of malignancy for cervical lymph nodes in patients followed up for differentiated thyroid cancer. J Clin Endocrinol Metab 2007;92:3590-4. 26. Danese D, Sciacchitano S, Farsetti A, Andreoli M, Pontecorvi A. Diagnostic accuracy of conventional versus sonography-guided fine-needle aspiration biopsy of thyroid nodules. Thyroid 1998;8:15-21. 27. Carmeci C, Jeffrey RB, McDougall IR, Nowels KW, Weigel RJ. Ultrasound-guided fine-needle aspiration biopsy of thyroid masses. Thyroid 1998;8:283-9. 28. Seiberling KA, Dutra JC, Gunn J. Ultrasound-guided fine needle aspiration biopsy of thyroid nodules performed in the office. Laryngoscope 2008;118:228-31. 29. Pacini F, Fugazzola L, Lippi F, Ceccarelli C, Centoni R, Miccoli P, et al. Detection of thyroglobulin in fine needle aspirates of nonthyroidal neck masses: a clue to the diagnosis of metastatic differentiated thyroid cancer. J Clin Endocrinol Metab 1992;74:1401-4. 30. Nikiforov YE, Steward DL, Robinson-Smith TM, Haugen BR, Klopper JP, Zhu Z, et al. Molecular testing for mutations in improving the fine-needle aspiration diagnosis of thyroid nodules. J Clin Endocrinol Metab 2009;94:2092-8. 31. Ertas B, Kaya H, Kurtulmus N, Yakupoglu A, Giray S, Unal OF, et al. Intraoperative ultrasonography is useful in surgical management of neck metastases in differentiated thyroid cancers. Endocrine 2015;48: 248-53. 32. Agcaoglu O, Aliyev S, Taskin HE, Aksoy E, Siperstein A, Berber E. The utility of intraoperative ultrasound in modified radical neck dissection: a pilot study. Surg Innov 2014;21:166-9. 33. Kim MK, Mandel SH, Baloch Z, Livolsi VA, Langer JE, Didonato L, et al. Morbidity following central compartment reoperation for recurrent or persistent thyroid cancer. Arch Otolaryngol Head Neck Surg 2004; 130:1214-6. 34. Karwowski JK, Jeffrey RB, McDougall IR, Weigel RJ. Intraoperative ultrasonography improves identification of recurrent thyroid cancer. Surgery 2002; 132:924-8; discussion 928-9. 35. Ahn D, Sohn JH, Kim H. Surgeon-performed intraoperative tumor localization in recurrent papillary 16
Hyun Jo Youn, et al.: Ultrasound in Thyroid Cancer thyroid carcinoma by ultrasound-guided intratumoral indigo carmine injection. World J Surg 2014;38:1995-2001. 36. Pacini F, Molinaro E, Castagna MG, Agate L, Elisei R, Ceccarelli C, et al. Recombinant human thyrotropin-stimulated serum thyroglobulin combined with neck ultrasonography has the highest sensitivity in monitoring differentiated thyroid carcinoma. J Clin Endocrinol Metab 2003;88:3668-73. 37. Tufano RP, Clayman G, Heller KS, Inabnet WB, Kebebew E, Shaha A, et al. Management of recurrent/ persistent nodal disease in patients with differentiated thyroid cancer: a critical review of the risks and benefits of surgical intervention versus active surveillance. Thyroid 2015;25:15-27. 38. Frasoldati A, Pesenti M, Gallo M, Caroggio A, Salvo D, Valcavi R. Diagnosis of neck recurrences in patients with differentiated thyroid carcinoma. Cancer 2003;97:90-6. 39. Torlontano M, Attard M, Crocetti U, Tumino S, Bruno R, Costante G, et al. Follow-up of low risk patients with papillary thyroid cancer: role of neck ultrasonography in detecting lymph node metastases. J Clin Endocrinol Metab 2004;89:3402-7. 40. Ko MS, Lee JH, Shong YK, Gong GY, Baek JH. Normal and abnormal sonographic findings at the thyroidectomy sites in postoperative patients with thyroid malignancy. AJR Am J Roentgenol 2010;194: 1596-609. 41. Torlontano M, Crocetti U, Augello G, D'Aloiso L, Bonfitto N, Varraso A, et al. Comparative evaluation of recombinant human thyrotropin-stimulated thyroglobulin levels, 131I whole-body scintigraphy, and neck ultrasonography in the follow-up of patients with papillary thyroid microcarcinoma who have not undergone radioiodine therapy. J Clin Endocrinol Metab 2006;91:60-3. 17